P1449: SAFETY PROFILE OF KETOROLAC CONTINUOUS INFUSION IN SICKLE CELL RELATED ACUTE VASO-OCCLUSIVE CRISIS
Authors: Valeria Maria Pinto, Barbara Gianesin, Salvatore Sardo, Filippo Mazzi, Giammarco Baiardi, Sofia Menotti, Fabio Piras, Gabriele Finco, Gian Luca Forni, Lucia De Franceschi
Journal: HemaSphere (2023)

Topic: 26. Sickle cell disease Background: Pain is the main symptom of acute vaso-occlusive crisis (VOCs) in patients with Sickle Cell Disease (SCD), requiring an early intensive analgesic treatment. We previously reported an algorithm for acute pain management of adult patients with SCD (Forni GL, et al. Orphanet J Rare Dis. 2014) based on multimodal analgesia protocol with continuous infusion of ketorolac and tramadol for 72 hours. However, safety data on ketorolac in adult SCD patient population are lacking, even if in hospital setting 1% incidence of hepatotoxicity and several cases of nephrotoxicity including acute and chronic renal failure have been described (S Hennessy, et al. Arch Intern Med. 1997). Aims: The aim of the study was to evaluate the impact of 72 hours continuous infusion of ketorolac and tramadol on liver, kidney function and coagulation parameters in SCD patients with acute sever VOCs defined by pai visual analog scale of >70/100 mm. Methods: This is a retrospective study. Data from clinical records of vaso-occlusive crises treated from 2011-2021 at two tertiary centers (Verona and Genoa) were collected. Patient privacy was protected through pseudonymization. The analgesia protocol consisted of a continuous infusion of ketorolac (0.9 mg/Kg/day) tramadol (7.2 mg/Kg/day), and metoclopramide (0.57 mg/Kg/day) in saline 0.9% at infusion rate by weight with an around the clock administration of a proton pump inhibitor. Multiple events were considered independent if they were separated in time by at least three weeks. Creatinine measurements were evaluated with multiple pairwise comparisons in order to detect any variations during ketorolac therapy and both the day of admission and the baseline value. Furthermore, a mixed linear model was built to study the time dependence of creatinine from time, gender, age, duration of ketorolac administration and variation of hemoglobin between the admission and the most recent stable value. For all measured biochemical parameters, the last evaluation was compared with the first day and basal determinations. For creatinine, eGFR ALT, and AST, a comparison with the measurements at 15 and 30 days. Results: Thirty-one patients were included in the analysis (38% males, age 33±10 years) for a total of 48 events included. The genotype distribution was: 20 (64%) SS, 9 S-beta (29%) and 2 SC (6%). The mean duration of therapy was 2.6±1.5 days. No differences were observed between the days of monitoring for creatinine and both the day 1 and basal (figure); the multivariate analysis showed a not significant dependence of creatinine by time; only gender was associated with creatinine values (p=0.013). The comparisons between the last evaluation with the one of the first day and the basal for all variables collected. Among the comparisons only AST approached the significance level of 0.05 for the comparison at the last day of evaluation and after 30 days. There was a statistically, but not clinically, significant increase of APTT between the first and last measurement (mean difference: 0.12 CI 95%: 0.24-0.22, p=0.012). Summary/Conclusion: Our study shows a safety profile of ketorolac in the absence of significant short term and long-term change in kidney and liver function as well as in coagulation parameters. in young adults with SCD, Thus, the use of ketorolac as part of the multimodal analgesia might represent a valuable strategy to limit the opioid exposure and to reduce the risk of opioid addition in patients with SCD.Keywords: Sickle cell disease, Vasoocclusive crisis, Sickle cell anemia